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Limited Systemic Sclerosis Patients with Pulmonary Arterial Hypertension Show Biomarkers of Inflammation and Vascular Injury

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  • Sarah A Pendergrass
  • Everett Hayes
  • Giuseppina Farina
  • Raphael Lemaire
  • Harrison W Farber
  • Michael L Whitfield
  • Robert Lafyatis

Abstract

Background: Pulmonary arterial hypertension (PAH) is a common complication for individuals with limited systemic sclerosis (lSSc). The identification and characterization of biomarkers for lSSc-PAH should lead to less invasive screening, a better understanding of pathogenesis, and improved treatment. Methods and Findings: Forty-nine PBMC samples were obtained from 21 lSSc subjects without PAH (lSSc-noPAH), 15 lSSc subjects with PAH (lSSc-PAH), and 10 healthy controls; three subjects provided PBMCs one year later. Genome-wide gene expression was measured for each sample. The levels of 89 cytokines were measured in serum from a subset of subjects by Multi-Analyte Profiling (MAP) immunoassays. Gene expression clearly distinguished lSSc samples from healthy controls, and separated lSSc-PAH from lSSc-NoPAH patients. Real-time quantitative PCR confirmed increased expression of 9 genes (ICAM1, IFNGR1, IL1B, IL13Ra1, JAK2, AIF1, CCR1, ALAS2, TIMP2) in lSSc-PAH patients. Increased circulating cytokine levels of inflammatory mediators such as TNF-alpha, IL1-beta, ICAM-1, and IL-6, and markers of vascular injury such as VCAM-1, VEGF, and von Willebrand Factor were found in lSSc-PAH subjects. Conclusions and Significance: The gene expression and cytokine profiles of lSSc-PAH patients suggest the presence of activated monocytes, and show markers of vascular injury and inflammation. These genes and factors could serve as biomarkers of PAH involvement in lSSc.

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  • Sarah A Pendergrass & Everett Hayes & Giuseppina Farina & Raphael Lemaire & Harrison W Farber & Michael L Whitfield & Robert Lafyatis, 2010. "Limited Systemic Sclerosis Patients with Pulmonary Arterial Hypertension Show Biomarkers of Inflammation and Vascular Injury," PLOS ONE, Public Library of Science, vol. 5(8), pages 1-13, August.
    • Handle: RePEc:plo:pone00:0012106
    DOI: 10.1371/journal.pone.0012106
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    References listed on IDEAS

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    1. Liu, Yufeng & Hayes, David Neil & Nobel, Andrew & Marron, J. S, 2008. "Statistical Significance of Clustering for High-Dimension, Low–Sample Size Data," Journal of the American Statistical Association, American Statistical Association, vol. 103(483), pages 1281-1293.
    2. Ausra Milano & Sarah A Pendergrass & Jennifer L Sargent & Lacy K George & Timothy H McCalmont & M Kari Connolly & Michael L Whitfield, 2008. "Molecular Subsets in the Gene Expression Signatures of Scleroderma Skin," PLOS ONE, Public Library of Science, vol. 3(7), pages 1-19, July.
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